What is mechanism of action?

mechanism of action is Cytochrome P450 2C9 Inducers [MoA], Cytochrome P450 2C19 Inducers [MoA], Cytochrome P450 3A4 Inducers [MoA], Cytochrome P450 1A2 Inducers [MoA] or Cytochrome P450 2B6 Inducers [MoA]

Carbamazepine Er

(Carbamazepine)

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Carbamazepine Er Prescribing Information

SERIOUS DERMATOLOGIC REACTIONS AND HLA-B*1502 ALLELE

SERIOUS AND SOMETIMES FATAL DERMATOLOGIC REACTIONS, INCLUDING TOXIC EPIDERMAL NECROLYSIS (TEN) AND STEVENS-JOHNSON SYNDROME (SJS), HAVE BEEN REPORTED DURING TREATMENT WITH CARBAMAZEPINE. THESE REACTIONS ARE ESTIMATED TO OCCUR IN 1 TO 6 PER 10,000 NEW USERS IN COUNTRIES WITH MAINLY CAUCASIAN POPULATIONS, BUT THE RISK IN SOME ASIAN COUNTRIES IS ESTIMATED TO BE ABOUT 10 TIMES HIGHER. STUDIES IN PATIENTS OF CHINESE ANCESTRY HAVE FOUND A STRONG ASSOCIATION BETWEEN THE RISK OF DEVELOPING SJS/TEN AND THE PRESENCE OF HLA-B*1502, AN INHERITED ALLELIC VARIANT OF THE HLA-B GENE. HLA-B*1502 IS FOUND ALMOST EXCLUSIVELY IN PATIENTS WITH ANCESTRY ACROSS BROAD AREAS OF ASIA. PATIENTS WITH ANCESTRY IN GENETICALLY AT-RISK POPULATIONS SHOULD BE SCREENED FOR THE PRESENCE OF HLA-B*1502 PRIOR TO INITIATING TREATMENT WITH CARBAMAZEPINE. PATIENTS TESTING POSITIVE FOR THE ALLELE SHOULD NOT BE TREATED WITH CARBAMAZEPINE UNLESS THE BENEFIT CLEARLY OUTWEIGHS THE RISK (SEE WARNINGS AND PRECAUTIONS, LABORATORY TESTS).

APLASTIC ANEMIA AND AGRANULOCYTOSIS

APLASTIC ANEMIA AND AGRANULOCYTOSIS HAVE BEEN REPORTED IN ASSOCIATION WITH THE USE OF CARBAMAZEPINE. DATA FROM A POPULATION-BASED CASE CONTROL STUDY DEMONSTRATE THAT THE RISK OF DEVELOPING THESE REACTIONS IS 5 TO 8 TIMES GREATER THAN IN THE GENERAL POPULATION. HOWEVER, THE OVERALL RISK OF THESE REACTIONS IN THE UNTREATED GENERAL POPULATION IS LOW, APPROXIMATELY SIX PATIENTS PER ONE MILLION POPULATION PER YEAR FOR AGRANULOCYTOSIS AND TWO PATIENTS PER ONE MILLION POPULATION PER YEAR FOR APLASTIC ANEMIA.

ALTHOUGH REPORTS OF TRANSIENT OR PERSISTENT DECREASED PLATELET OR WHITE BLOOD CELL COUNTS ARE NOT UNCOMMON IN ASSOCIATION WITH THE USE OF CARBAMAZEPINE, DATA ARE NOT AVAILABLE TO ESTIMATE ACCURATELY THEIR INCIDENCE OR OUTCOME. HOWEVER, THE VAST MAJORITY OF THE CASES OF LEUKOPENIA HAVE NOT PROGRESSED TO THE MORE SERIOUS CONDITIONS OF APLASTIC ANEMIA OR AGRANULOCYTOSIS.

BECAUSE OF THE VERY LOW INCIDENCE OF AGRANULOCYTOSIS AND APLASTIC ANEMIA, THE VAST MAJORITY OF MINOR HEMATOLOGIC CHANGES OBSERVED IN MONITORING OF PATIENTS ON CARBAMAZEPINE ARE UNLIKELY TO SIGNAL THE OCCURRENCE OF EITHER ABNORMALITY. NONETHELESS, COMPLETE PRETREATMENT HEMATOLOGICAL TESTING SHOULD BE OBTAINED AS A BASELINE. IF A PATIENT IN THE COURSE OF TREATMENT EXHIBITS LOW OR DECREASED WHITE BLOOD CELL OR PLATELET COUNTS, THE PATIENT SHOULD BE MONITORED CLOSELY. DISCONTINUATION OF THE DRUG SHOULD BE CONSIDERED IF ANY EVIDENCE OF SIGNIFICANT BONE MARROW DEPRESSION DEVELOPS

Initial:

On the first day, either 100 mg twice a day for tablets or extended-release tablets, or ½ teaspoon four times a day for suspension, for a total daily dose of 200 mg. This daily dose may be increased by up to 200 mg/day using increments of 100 mg every 12 hours for tablets or extended-release tablets, or 50 mg (½ teaspoon) four times a day for suspension, only as needed to achieve freedom from pain. Do not exceed 1200 mg daily.

Maintenance:

Control of pain can be maintained in most patients with 400 to 800 mg daily. However, some patients may be maintained on as little as 200 mg daily, while others may require as much as 1200 mg daily. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.

Dosage Information
	Initial Dose			Subsequent Dose			Maximum Daily Dose
Indication	Tablet*	Extended-release tablet†	Suspension	Tablet*	Extended-release tablet†	Suspension	Tablet*	Extended-release tablet†	Suspension
Epilepsy Under 6 yr	10-20 mg/kg/day twice a day or 3 times a day		10-20 mg/kg/day 4 times a day	Increase weekly to achieve optimal clinical response, 3 times a day or 4 times a day		Increase weekly to achieve optimal clinical response, 3 times a day or 4 times a day	35 mg/kg/24 hr (see Dosage and Administration section above)		35 mg/kg/24 hr (see Dosage and Administration section above)
6-12 yr	100 mg twice a day (200 mg/day)	100 mg twice a day (200 mg/day)	½ tsp 4 times a day (200 mg/day)	Add up to 100 mg/day at weekly intervals, 3 times a day or 4 times a day	Add 100 mg/day at weekly intervals, twice a day	Add up to 1 tsp (100 mg)/day at weekly intervals, 3 times a day or 4 times a day	1000 mg/24 hr
Over 12 yr	200 mg twice a day (400 mg/day)	200 mg twice a day (400 mg/day)	1 tsp 4 times a day (400 mg/day)	Add up to 200 mg/day at weekly intervals, 3 times a day or 4 times a day	Add up to 200 mg/day at weekly intervals, twice a day	Add up to 2 tsp (200 mg)/day at weekly intervals, 3 times a day or 4 times a day	1000 mg/24 hr (12-15 yr) 1200 mg/24 hr (>15 yr) 1600 mg/24 hr (adults, in rare instances)
Trigeminal Neuralgia	100 mg twice a day (200 mg/day)	100 mg twice a day (200 mg/day)	½ tsp 4 times a day (200 mg/day)	Add up to 200 mg/day in increments of 100 mg every 12 hr	Add up to 200 mg/day in increments of 100 mg every 12 hr	Add up to 2 tsp (200 mg)/day in increments of 50 mg (½ tsp) 4 times a day	1200 mg/24 hr

*Tablet = Chewable or conventional tablets.

^†Extended-release tablet = Carbamazepine extended-release tablets.

Carbamazepine should not be used in patients with a history of previous bone marrow depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. Likewise, on theoretical grounds its use with monoamine oxidase (MAO) inhibitors is not recommended. Before administration of carbamazepine, MAO inhibitors should be discontinued for a minimum of 14 days, or longer if the clinical situation permits.

Coadministration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Coadministration of carbamazepine with nefazodone is contraindicated.

If adverse reactions are of such severity that the drug must be discontinued, the physician must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to seizures or even status epilepticus with its life-threatening hazards.

The most severe adverse reactions have been observed in the hemopoietic system and skin (see BOXED WARNING), the liver, and the cardiovascular system.

The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting. To minimize the possibility of such reactions, therapy should be initiated at the lowest dosage recommended.

The following additional adverse reactions have been reported:

Hemopoietic System

Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda.

Skin

: TEN and SJS (see BOXED WARNING), Acute Generalized Exanthematous Pustulosis (AGEP), pruritic and erythematous rashes, urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia, diaphoresis, onychomadesis and hirsutism. In certain cases, discontinuation of therapy may be necessary.

Cardiovascular System

Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism (e.g., pulmonary embolism), and adenopathy or lymphadenopathy.

Some of these cardiovascular complications have resulted in fatalities. Myocardial infarction has been associated with other tricyclic compounds.

Liver

Abnormalities in liver function tests, cholestatic and hepatocellular jaundice, hepatitis, very rare cases of hepatic failure.

Pancreatic: Pancreatitis.

Respiratory System:

Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis, or pneumonia.

Genitourinary System:

Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, renal failure, and impotence. Albuminuria, glycosuria, elevated BUN, and microscopic deposits in the urine have also been reported. There have been rare reports of impaired male fertility and/or abnormal spermatogenesis.

Testicular atrophy occurred in rats receiving carbamazepine orally from 4 to 52 weeks at dosage levels of 50 to 400 mg/kg/day. Additionally, rats receiving carbamazepine in the diet for 2 years at dosage levels of 25, 75, and 250 mg/kg/day had a dose-related incidence of testicular atrophy and aspermatogenesis. In dogs, it produced a brownish discoloration, presumably a metabolite, in the urinary bladder at dosage levels of 50 mg/kg and higher. Relevance of these findings to humans is unknown.

Nervous System:

Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, hyperacusis, neuroleptic malignant syndrome.

There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency, but the exact relationship of these reactions to the drug has not been established.

Isolated cases of neuroleptic malignant syndrome have been reported both with and without concomitant use of psychotropic drugs.

Digestive System:

Nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation, anorexia, and dryness of the mouth and pharynx, including glossitis and stomatitis.

Eyes:

Scattered punctate cortical lens opacities, increased intraocular pressure (see WARNINGS, General) as well as conjunctivitis, have been reported. Although a direct causal relationship has not been established, many phenothiazines and related drugs have been shown to cause eye changes.

Musculoskeletal System:

Aching joints and muscles, and leg cramps.

Metabolism:

Fever and chills. Hyponatremia (see WARNINGS, General). Decreased levels of plasma calcium have been reported. Osteoporosis has been reported.

Isolated cases of a lupus erythematosus-like syndrome have been reported. There have been occasional reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking anticonvulsants.

A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine.

Carbamazepine USP, is an anticonvulsant and specific analgesic for trigeminal neuralgia, available for oral administration as extended-release tablets of 100, 200, and 400 mg. Its chemical name is 5H-dibenz [b, f] azepine-5-carboxamide, and its structural formula is:

Referenced Image

Carbamazepine USP is a white to off-white powder, practically insoluble in water and soluble in alcohol and in acetone. Its molecular weight is 236.27g/mol.

Inactive Ingredients

: cellulose compounds, dextrates, magnesium stearate, mannitol, polyethylene glycol, sodium lauryl sulfate, titanium dioxide, talc, iron oxide yellow.

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Carbamazepine Er

Carbamazepine Er Prescribing Information

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